rs3833748

Positions:

• chr11-72190417-TC-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The ENST00000378140.3(ENSG00000204971):​n.419+8095del variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0382 in 152,212 control chromosomes in the GnomAD database, including 208 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.038 (208 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ENST00000378140.3 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.388

Genes affected

FOLR1 (HGNC:3791): (folate receptor alpha) The protein encoded by this gene is a member of the folate receptor family. Members of this gene family bind folic acid and its reduced derivatives, and transport 5-methyltetrahydrofolate into cells. This gene product is a secreted protein that either anchors to membranes via a glycosyl-phosphatidylinositol linkage or exists in a soluble form. Mutations in this gene have been associated with neurodegeneration due to cerebral folate transport deficiency. Due to the presence of two promoters, multiple transcription start sites, and alternative splicing, multiple transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Oct 2009]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0898 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FOLR1	NM_000802.3	c.-9+491del		intron_variant			NP_000793.1
FOLR1	NM_016724.3	c.-74-154del		intron_variant			NP_057936.1
FOLR1	NM_016725.3	c.-9+663del		intron_variant			NP_057937.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
	ENST00000378140.3	n.419+8095del		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0381 AC: 5802 AN: 152094 Hom.: 206 Cov.: 32

Gnomad AFR AF: 0.0923

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.0197

Gnomad ASJ AF: 0.0248

Gnomad EAS AF: 0.0788

Gnomad SAS AF: 0.0648

Gnomad FIN AF: 0.0134

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.00961

Gnomad OTH AF: 0.0311

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 18 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 16

Gnomad4 AFR exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0382 AC: 5809 AN: 152212 Hom.: 208 Cov.: 32 AF XY: 0.0392 AC XY: 2917 AN XY: 74434

Gnomad4 AFR AF: 0.0922

Gnomad4 AMR AF: 0.0196

Gnomad4 ASJ AF: 0.0248

Gnomad4 EAS AF: 0.0788

Gnomad4 SAS AF: 0.0647

Gnomad4 FIN AF: 0.0134

Gnomad4 NFE AF: 0.00963

Gnomad4 OTH AF: 0.0303

Alfa AF: 0.0263 Hom.: 8

Bravo AF: 0.0408

Asia WGS AF: 0.0560 AC: 196 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3833748; hg19: chr11-71901461;